Increasing health issues related to immune and gut function such as inflammatory disorders, resistance to infections and metabolic syndrome demand modern analytical approaches to accelerate nutritional research aimed at health promotion and disease prevention. Gut microbial-human mutualism endows the host ‘superorganism’ with a fitness advantage including nutritional, immune and intestinal health aspects. The gut microbiome enlarges our genome and enhances our metabolic potential. Dietary modulation can significantly alter the microbiota community and metabolic activity, and consequently impacts on nutrient bioavailability and host metabolism. Although in an early stage, microbial metabolites generated during colonic fermentation of food stuffs may have beneficial or deleterious effects on intestinal health and immunity, as summarized in this review. However, current evidence is largely based on in vitro and animal studies while substantiation in humans is lacking. The challenge to establish coherent links between the bioconversion of non-digestible food ingredients, their bioavailability and their downstream effects on the host metabolism may be achieved by metabolomics. In this review, metabolomics studies focusing on microbe-host mutualism have demonstrated that metabolomics is capable of detecting and tracking diverse microbial metabolites from different non-digestible food ingredients, of discriminating between phenotypes with different inherent microbiota and of potentially diagnosing infection and gastrointestinal diseases. Integrative approaches such as the combined analysis of the metabolome in different biofluids together with other -omics technologies will cover exogenous and endogenous effects and hence show promise to generate novel hypotheses for innovative functional foods impacting gut health and immunity.